[2] Tirico has called a multitude of sports in his career, including the NBA, NHL, college football and basketball, golf, tennis, and World Cup soccer.

Tirico was one of the subjects covered in Mike Freeman's 2000 book ESPN: An Uncensored History, where accounts of misconduct involving him sexually harassing and stalking at least six women led to an employment suspension for three months in 1992.

[19][20] On May 9, 2016, after a leak the prior month, it was officially announced that Mike Tirico would join NBC Sports effective July 1, 2016.

[23] Tirico served as a studio host and contributor for NBC's broadcasts of the 2016 Summer Olympics from Rio de Janeiro in August.

[21] Richard Deitsch of Sports Illustrated suggested that Tirico could potentially succeed Bob Costas as the primetime host of NBC's Olympics coverage.

NBC Sports chairman Mark Lazarus explained following the 2014 Winter Olympics that the division had begun to "think about what life after Bob might be, whether post-Rio, post-Pyeongchang, post-Tokyo, whenever he does not want to do it anymore."

[24] The NFL later stated that its contract with NBC required that the network use its lead play-by-play commentator for all primetime broadcasts nationally over-the-air.

[28][29] Consequently, he only called to two late-season games in the Thursday Night Football package produced for NFL Network, held on a Saturday and Christmas Sunday respectively, with Doug Flutie and Tony Dungy.

[33][34][35][36] On May 31, 2017, it was announced that Mike Tirico would permanently replace Al Michaels as the play-by-play commentator for all of NBC's Thursday Night Football games.

[37] Starting that year, he took over the role of Tom Hammond in Triple Crown coverage[38] and became full-time as the play-by-play announcer for Notre Dame football.

[39] Tirico skipped Super Bowl LII in order to focus on preparing for the 2018 Winter Olympics, which began the following Friday, but contributed to NBC's pregame coverage from Pyeongchang.

[43] On February 20, 2019, Tirico called his first NHL game on NBCSN's Wednesday Night Hockey, between the Chicago Blackhawks and Detroit Red Wings, joined by Eddie Olczyk on color commentator and Brian Boucher as the "Inside-the-Glass" reporter.

Due to the ongoing COVID-19 pandemic, NBC decided to give Michaels 3–5 "bye weeks", in order to minimize travel.

[55] Tirico has been paired in the college football booth with Tim Brant,[56] Terry Bowden,[57] Mike Gottfried,[58] Kirk Herbstreit, Lee Corso, and David Norrie.

Since the beginning of the 2017 season, Tirico has served as play-by-play for Notre Dame Football on NBC, partnering with Doug Flutie and later Tony Dungy.

On April 21 and 22, 2007, he appeared as a guest host, filling in for Michael Wilbon, alongside Tony Kornheiser on ESPN's Pardon the Interruption.