Vlasic played 19 seasons for the San Jose Sharks before he was placed on waivers June 26, 2025, for the purpose of buying out his contract. He had one season remaining on an eight-year, $56 million contract ($7 million average annual value) he signed with San Jose on July 1, 2017. He left as the Sharks' leader among defensemen in games played (1,323) and second to Brent Burns in goals (84), assists (295) and points (379).

Selected by the Sharks in the second round (No. 35) in the 2005 NHL Draft, the defenseman affectionately nicknamed "Pickles" was an instant hit in 2006-07 and became a regular at age 19. He played his 1,200th NHL game, all for the Sharks, on Jan. 1, 2023.

Vlasic led NHL rookies in ice time (22:12) and was third on the Sharks. He was named to the NHL All-Rookie Team along with teammate Matt Carle, the first defensemen from the same team to sweep the all-rookie spots since Nicklas Lidstrom and Vladimir Konstantinov of the Detroit Red Wings in 1991-92.

Vlasic's durability is also impressive; he played 253 consecutive games from Jan. 15, 2007 through Jan. 28, 2010.

He tied for the Sharks lead with a plus-21 rating in 2009-10 and led them in blocked shots in 2010-11 with 147. He was again tops on San Jose with 171 blocked shots in 2011-12, and had eight blocks in a game against the Los Angeles Kings on Dec. 23, 2011.

On March 20, 2013, against the Edmonton Oilers, Vlasic became the fourth defenseman to play 500 games with the Sharks, following Mike Rathje, Marcus Ragnarsson and Scott Hannan.

Following a solid 2013-14 season, when he tied for ninth in the NHL at plus-31, Vlasic received votes for the Norris and Lady Byng trophies. He was also a key player when the Sharks reached their first Stanley Cup Final in 2016.

Vlasic reached double figures in goals for the first time in 2017-18, scoring 11 times and finishing with 32 points.

Before coming to the NHL, Vlasic won the Memorial Cup with Quebec of the Quebec Major Junior Hockey League in 2005-06. In three seasons with Quebec, he scored 22 goals and 113 points and was plus-86. Quebec retired his No. 44 on March 20, 2016.