Hasler began his first grade career with the Penrith Panthers in 1982, but quickly transferred to the Manly Warringah Sea Eagles. Hasler’s contact with Manly came by chance.

After having played only 12 games for the Penrith Panthers in 1982 and 1983, Bob Fulton, on the lookout for a halfback due to not being satisfied with the play of Phil Blake, offered Hasler a trial at Manly and he signed to play for the Sea Eagles in 1984.

Hasler’s value as a utility player led to his frequent selection on the bench in representative football. Hasler played 13 State of Origin matches for New South Wales (7 from the bench, 3 at halfback, 2 at five-eighth and 1 at lock), scoring 2 tries during these games. His biography, The Utility Player, was written by prominent Australian author and Manly Warringah fan Thomas Keneally and was published in 1993.

After the 1993 season, Hasler spent the off-season playing for Hull F.C. in the English Rugby League Premiership. He later returned to the Sea Eagles for the 1995 and 1996 ARL season. Hasler had a new role for the season playing mostly at hooker. Although starting the 1996 season as the teams hooker, the signing of 1994 Kangaroo Tour hooker Jim Serdaris saw Hasler play most of the season from the bench for the Sea Eagles. The team had another great year, winning their second straight minor premiership before going on to defeat St. George 20–8 in the Grand Final at the Sydney Football Stadium, giving Hasler his second and last premiership win as a player.

In 2004, Des Hasler was appointed head coach of the Manly Warringah Sea Eagles. In the 2005, 2006 and 2007 seasons he led the team to the semi-finals for the first time since the late 1990s. Hasler gained the experience of Geoff Toovey as assistant coach in the 2007 season. The team was a contender in the 2007 National Rugby League premiership, and finished second on the NRL ladder, losing the grand final 34–8 Melbourne Storm.

In 2008, he was named the Rugby League International Federation’s Coach of the Year at the RLIF Awards.

After failing to win the 1987 World Club Challenge with Manly as a player, he won it with them as coach in 2009.

He took Manly to the finals again in 2009 and 2010, but lost a final in each year to be eliminated from the finals.

He coached his 200th first-grade game on 13 August 2011 when Manly defeated their traditional rivals Parramatta 26–20 at Parramatta Stadium. The win was also Hasler’s 117th win as a coach.

In 2011, Manly finished second on the NRL ladder. Manly defeated North Queensland 42–8 at the Sydney Football Stadium for their first finals win since 2008. Manly went on to win the 2011 NRL Grand Final. He was named coach of the year at the RLIF Awards.

Hasler joined Canterbury on 14 November 2011 as head coach for the 2012 NRL season. He had immediate success as he took the club to finish eight places better than the previous season to the top of the ladder and collected the minor premiership. After impressive Qualifying Final and Preliminary Final wins; 16–10 over former club Manly-Warringah Sea Eagles and 32–8 over South Sydney Rabbitohs respectively, the club were beaten in the Grand Final by the Melbourne Storm 14–4. At the 2012 Dally M Awards Hasler was named the NRL’s coach of the year.

A week after leading Manly to the 2011 premiership, Hasler signed to coach the Canterbury-Bankstown Bulldogs in the 2013 season. He initially agreed to continue to coach Manly for the 2012 season, but on 11 November 2011, Manly’s board of directors sacked him, alleging “serious breaches” of his contract with rumors rife of the breaches including enticing staff and players to join him at the Bulldogs from 2013. A number of Manly’s coaching and administrative employees had announced they would be joining Hasler at Canterbury.

In the 2014 NRL season, Hasler led Canterbury to the 2014 NRL Grand Final, and lost 30-6 to South Sydney at ANZ Stadium.

In the 2016 NRL season Canterbury finished two places lower than the previous season as they finished in seventh place, the same position they managed to reach the Grand Final from two years earlier, but those hopes of a 2014 repeat were crushed in the qualifying elimination final where the Bulldogs after leading 6–4 at half-time but suffered a 28–12 defeat by the Penrith Panthers at the Sydney Football Stadium after which straight away Canterbury bowed out of the finals series.

On 19 September 2017, it was announced by the Canterbury-Bankstown Bulldogs that Hasler had been released. On 1 December 2017, it was announced that Hasler was taking Canterbury to court and was seeking $2 million in damages after he was terminated by the club despite signing a two-year contract extension earlier in the season.

On 4 May 2018 Hasler and Canterbury-Bankstown reached an out of court settlement for an undisclosed sum of money. Canterbury issued a statement saying “After a great deal of discussion over the last couple of months, The Bulldogs are pleased to have reached an agreement with Des Hasler, It was important for the club to be able to bring this matter to a close and move forward. Our members and fans deserve that”.

On 22 October 2018, Hasler was announced as the new head coach of Manly for the 2019 season.

Hasler would guide Manly to the second week of the finals series in 2019 as the club were defeated by South Sydney 34-26 in the elimination semi-final at ANZ Stadium.