Michalak’s club Stade Toulousain were crowned the champions of France in 2001 when they defeated Montferrand in the final 34–22. Later that year, in November, Michalak made his international debut for France, coming on as a replacement in a match against South Africa in Paris at the national stadium, Stade de France. France won the match 20–10. He was then promoted to the starting line-up for a test against Australia the following week in Marseille by head coach Bernard Laporte. Michalak played the match at scrum-half and scored his first points for France in the match, landing one penalty goal. France won the match by one point, 14–13. He was used as a replacement in the subsequent match against Fiji at Saint-Étienne, which France also won.

In 2003 he started at scrum-half for France in their Six Nations match against Italy in Rome at Stadio Flaminio. France won the match with Michalak also scoring his first try for the national team. He played in one other Six Nations match that year, starting against Wales in Paris, where he scored another try in the 33–5 victory. Toulouse proceeded to win the 2002–03 Heineken Cup, defeating fellow French team USA Perpignan 22–17 in the final. Michalak was then included in the national squad for the June tests prior to the 2003 World Cup in Australia. He was not used in France’s first match against Argentina, but came off the bench in the second of two. He then started in the following match against the All Blacks, where he scored eight points with his kicking in the loss. He earned subsequent caps in matches against Romania, scoring 14 points with his boot, and against England where he scored 12 of France’s 17 points in the one point victory.

The following year, Michalak played in four of France’s Six Nations fixtures all in the starting line-up. He was not used in the match against Italy. Toulouse also made it to the final of the 2003–04 Heineken Cup, though they were defeated by the London Wasps. Michalak gained four more caps in November 2004 against Argentina, Australia and the All Blacks. He played in all of France’s 2005 Six Nations matches, as well as Toulouse’s 2004–05 Heineken Cup victory over Stade Français. He came into the Heineken Cup final under an injury cloud, but showed no signs of it, even sealing the victory for Toulouse in the end with a late drop goal, having also scored two earlier penalties. Toulouse won 18–12 and became the first ever team to win the Cup three times. He was then capped three times in June for France; twice against the Springboks and once against Australia. Michalak was capped another four times in November, against Australia, Canada, Tonga and South Africa. He was named in France’s squad for the 2007 Rugby World Cup. Within seconds of coming as a substitute on in the quarter-finals of the tournament, he made a break and then made an uncalled forward pass to Yannick Jauzion who scored a try which when converted gave France a two-point lead which they held onto to beat New Zealand, the tournament favourites. Wayne Barnes missed this call, and has been critcised heavily since.

Michalak signed with The Sharks for the Super 14 in 2008. The team, who had previously signed former French internationals Thierry Lacroix and Olivier Roumat, saw him as a key player in the Currie Cup campaign of the Sharks, the provincial side that operates the Super Rugby side. Michalak made his Super 14 debut against the Stormers. but featured in only nine games before being sidelined by injury and shortly thereafter ending his spell with The Sharks. He played in the 2008 Currie Cup final, helping the Sharks to win and becoming the third Frenchmen, after Olivier Roumat and Thierry Lacroix to win a Currie Cup medal. Michalak re-signed with his former club Toulouse for the start of the 2008–09 season.

Michalak’s second spell with Toulouse was frustrated by injury with two serious injuries that limited his appearances for his club. In March 2010, in a match against rivals Stade Français, Michalak tore cruciate ligaments in a knee and was stretchered off. The injury was expected to sideline him for up to one year.

In 2011, he participated in Rendez-vous en terre inconnue. In 2019, Frédéric Michalak continued his studies at EM Lyon Business School.

On 31 May 2011 it was announced that Michalak had signed a one-year contract with the Sharks, effective immediately—which meant that Michalak would not play in Toulouse’s Top 14 final on 4 June. The Sharks’ need to fill vacancies left by injuries to several of their scrumhalves is widely considered a key short-term motive for the signing; in the 2012 season, he is seen as an extra option at fly-half, a position where they had issues in 2011. Michalak’s final match with the Sharks was the 2012 Super Rugby final against the Chiefs. It was not a memorable occasion for Michalak, as the Chiefs won convincingly 37–6.

After over two years out of international rugby, Michalak was recalled by new coach Philippe Saint-André for the 2012 mid-year test series in Argentina. He came on as a replacement in the first test, which France lost 23–20, but started at fly-half for the second test. France won 49–10, and Michalak scored 19 points. In April 2012, Top 14 club Toulon confirmed that Michalak would be joining on a two-year deal.

In August 2012, Michalak admitted that the prospect of playing for France again was the key reason for his return:

During France’s 2015 World Cup warm-up against England on 22 August, he surpassed Christophe Lamaison as France’s all-time leading point scorer.

During France’s 2015 World Cup match against Canada on 1 October 2015, Michalak became France’s all-time leading Rugby World Cup points scorer.