Jesse Scanzano participated in the evaluation camp for the senior 2010–11 Canadian national women's team. Scanzano played for Canada White (the camp was divided into four teams, Red, White, Yellow, Blue). Bailey Bram, Christine Bestland and Meghan Agosta played for Canada Yellow. Vicki Bendus played for Canada Blue.
August 27: Meghan Agosta was announced as a finalist for the Women’s Sports Foundation’s 2010 Sportswoman of the Year Team Award. It is awarded to the top female athlete (NCAA, Olympic, professional) who has demonstrated exceptional play in helping her team win a championship.
September 9: Head coach Michael Sisti appointed Meghan Agosta as team captain. Vicki Bendus and Jesse Scanzano are alternate captains.
On September 12, 2010, Lakers assistant coach Kristen Cameron sustained a serious spinal cord injury which was given immediate medical care at Hamot Medical Center in Erie, Pennsylvania. She was hit by a car and thrown 15 metres off her bicycle. During the 2010–11 Mercyhurst Lakers women's ice hockey season, the Lakers wore a patch on their jerseys with the initials K.C.10-11.
September 28: In the USA Today/USA Hockey Magazine Women's College Hockey Poll, the Lakers have been voted as the pre-season Number 3.
October 1: Meghan Agosta joined Jesse Scanzano as only the second Mercyhurst player to have 100 career assists. She picked up the assist in the second period.
October 15: Bailey Bram registered two assists, including her 100th career point, in a game against the Bemidji State Beavers. She became the 11th Lakers player to crack the century mark in the 4-0 win.  Junior Hillary Pattenden recorded her first shutout of the season and seventh career in the 4-0 win.
October 16: With the loss against Bemidji State, the Lakers endured their first regular-season road loss in 38 games dating back to the end of the 2007-08 season.
As the Lakers went 6-1-0 in October 2010, Bestland scored four goals, including two in a 7-3 defeat of the Robert Morris Colonials. In addition, she had six as¬sists. In her first game as a Laker, she scored a goal. She registered points in five of the seven games played and finished the month with a plus/minus rating of +13. For her efforts, she was recognized as College Hockey America’s Rookie of the Month.
October 29 marked the CHA opening game for both the Mercyhurst Lakers and Robert Morris Colonials. Meghan Agosta scored two goals and notched an assist in a 7-3 defeat of the Colonials. Agosta’s goals came during a six-goal first period for the Lakers, and her two goals were separated by just 20 seconds. The goals happened at the 19:27 and 19:47 marks. With the two scores, Agosta now has 20 career goals against the Colonials. For the month of October, Agosta scored 10 goals and had 19 points. 
Nov. 2 and 6: Bailey Bram led the Lakers in scoring with four goals. Bram posted her third career hat trick in a game versus second-ranked Cornell. With the hat trick, Bram surpassed the 50-goal career plateau at Mercyhurst. A few days later, Bram scored another goal versus Niagara. For her efforts, she was recognized as the CHA Player of the Week.
On December 3-4, 2010, Christine Bestland scored three goals and had two assists as the Lakers swept the Purple Eagles for the first time since the 2008-09 season. She stretched her scoring streak to a career-long three games in Saturday’s 7-2 victory.  Vicki Bendus led all skaters with six points in the Lakers' two-game sweep of Niagara. She scored a goal in each game and accumulated four assists.  Stephanie Ciampa of Mercyhurst earned her second career win on December 3. Mercyhurst had a 6-1 win over the Purple Eagles. She recorded eight saves and allowed one goal in the final minutes after holding Niagara scoreless for nearly 57minutes. She is now 2-0-0 in her career at the college. 
December 10-11: In a two game series versus St. Lawrence, Agosta scored three goals and added four assists. In the December 11 win, she scored two goals and assisted on three others to help the Lakers defeat the Skating Saints by a 7-3 score. The five-point performance marked a season-high for points in a game in the season. In addition, she moved her season total to 38, which ranks first in the NCAA.
On January 14 and 15, Bailey Bram combined for nine points in the two wins over Brown. In the first win, Bram accumulated three assists for a 6-0 score. The following day, she registered two goals and four assists for a career-high six points. In addition, Mercyhurst notched 12 goals in a game for the first time since the 1999-2000 season. Rookie Christie Cicero scored two goals and two assists in the series. In each game she registered a goal and an assist. For the season, she has registered seven goals and five assists.
Jan 18: Senior Karlee Overguard scored twice, while freshman Lauren Slebodnick made 24 saves to secure a 3-0 victory at Mercyhurst. The win for Cornell avenged the only loss for the Big Red on the season, a 4-3 loss to the Lakers back in November at Lynah Rink. The other goal for the Big Red was scored by Catherine White. The Big Red went scoreless in four power-play opportunities, but successfully killed three penalties. For Mercyhurst, Hillary Pattenden stopped 29 of the 32 shots she faced on the night in taking the loss. 
January 21-22: Christine Bestland tied teammates Meghan Agosta and Jesse Scanzano with five points in the two-game sweep of the Robert Morris Colonials. She scored two goals and added three assists to increase her point total to 35 on the season. On the 21st, she scored two goals and helped out on another. Meghan Agosta scored a goal and dished out two assists. The following day, Bestland assisted on two goals as the Lakers scored seven goals against Robert Morris for the second time this season. Agosta she scored her 26th of the season while the Lakers were short-handed, and added an assist. By defeating the Robert Morris Colonials on January 22, the Lakers have now won 20 games for the 10th straight season. The season series against the Colonials is now 26-0-0 all-time. Agosta is now just seven points away from breaking former Harvard player Julie Chu’s mark of 285 points to become the NCAA all-time points leader.  Hillary Pattenden picked up both wins in the series with 18 saves in the first game and 25 in the second. She improves to 18-5-0 on the season.
Meghan Agosta was featured in Sports Illustrated's Faces in the Crowd feature in the the February 21, 2011 issue (as recognition of becoming the all-time NCAA scorer).