Apart from tennis, Andreas loves skiing and is an AC Milan fan, he is a native German speaker and also fluently speaks Italian and English.

In addition, he qualified for his first two ATP events at the 2003 Generali Open in Kitzbühel and in Bucharest, where he was defeated by Olivier Mutis and José Acasuso, respectively.

In the Davis Cup, Seppi came back from two sets to love down and defeated Juan Carlos Ferrero, before losing to Rafael Nadal in the reverse singles.

After this performance, he reached his first ATP Tour semifinal in Palermo, where he defeated defending champion Tomáš Berdych, before falling to Igor Andreev.

In 2006, Seppi made semifinals on hard courts in Sydney and grass in Nottingham, showing that he was able to perform well on other surfaces besides clay.

Seppi ended the streak of four consecutive Sydney titles for Lleyton Hewitt and, in the process, saved two match points.

Seppi made the final of the Sunrise Challenger, defeating Gustavo Kuerten, Juan Martín del Potro, and Nicolás Massú, and then losing to Gaël Monfils.

He surprisingly made his first ATP Tour final in Gstaad, where he defeated Stefan Koubek and Igor Andreev both in third-set tiebreakers.

In the 2008 season Seppi won his first Challenger title at Bergamo where he defeated Julien Benneteau in the final for the loss of 1 set in the tournament.

Seppi made the semifinals of the 2008 Hamburg Masters, this was the first time he reached that stage of the Masters Series events, he defeated Richard Gasquet, Juan Mónaco and Nicolas Kiefer in a match where he led 6–3, 5–3 before winning which included Seppi winning the last 4 games and went for 3 hours and 13 minutes in duration,[8] before losing to Roger Federer in the semi-finals.

In 2009 Seppi made the semifinals in Belgrade and in Umag both on clay, while winning his second Challenger title in San Marino defeating countryman Potito Starace in the final.

En route the quarterfinals at the 2012 Rome Masters, he defeated Stanislas Wawrinka in the third round, having saved six match points in the process.

At the 2014 Monte-Carlo Rolex Masters Seppi defeated no.13 seed Mikhail Youzhny and Pablo Andújar but lost to Rafael Nadal in the third round.

In January at the 2015 Australian Open, the unseeded Seppi caused a huge upset by beating second seed and four-time champion Roger Federer in the third round in four sets, after having lost to him in ten previous meetings.

[22] In June, at the 2015 Gerry Weber Open, Roger Federer took his revenge for the earlier in the year loss over Seppi by winning the title.

He started off with a decent result in the 2016 Australian Open, as the 28th seed he managed to get to the third round before losing to eventual champion Novak Djokovic.

In 2016 Wimbledon Championships, Seppi smashed Guillermo García López in straight sets before losing to eventual finalist Milos Raonic in the second round.

Seppi then gained a spot in the main draw as lucky loser, where he defeated João Sousa in three sets at first round.

In the quarterfinals, he defeated Daniil Medvedev to reach the semifinals, but lost to the newly returned to the No.1 position in the ATP rankings, Roger Federer in straight sets, failing to get the spot in the final.

He won his tenth title at the 2021 Biella Challenger Indoor III becoming at the age of 37, the oldest champion from Italy in the history of the circuit.

[25] At the 2021 US Open he reached the second round after a five setter with a final set tiebreak 2–6, 7–5, 6–4, 2–6, 7–6(13) where he defeated Márton Fucsovics, saving 5 match points.

[3][30][31][32] Only main-draw results in ATP Tour, Grand Slam tournaments, Davis Cup/ATP Cup/Laver Cup and Olympic Games are included in win–loss records.