Monaco started 2010 with the Heineken Open, where he defeated Horacio Zeballos in the first round, but lost to eventual champion John Isner in three sets.
He lost to sixth seed Nikolay Davydenko in the third round of the 2010 Australian Open, having defeated Ernests Gulbis and Michaël Llodra in five sets.
He lost to Thomaz Bellucci in the final of the 2010 Movistar Open, after defeating Nicolas Massú, Juan Ignacio Chela, Peter Luczak, and João Souza.
He lost to Juan Carlos Ferrero in the semifinals of the 2010 Copa Telmex just hours after defeating Horacio Zeballos in the quarterfinals, where he did not face a single break point.
He also defeated Juan Ignacio Chela in the second round and Łukasz Kubot.
He lost to Juan Carlos Ferrero in the semifinals of the 2010 Abierto Mexicano Telcel, retiring with an abdominal strain.
He defeated top seed Fernando Verdasco in the quarterfinals, Juan Ignacio Chela for the second time in as many weeks, and Alberto Martín.

He defeated Fabio Fognini in the second round of the 2010 BNP Paribas Open.
He then faced Juan Carlos Ferrero in the third round; this was their third straight meeting, with Ferrero prevailing in the other two.
He upset Ferrero for the first time in a match than lasted over 3 hours.
He then defeated Guillermo García-López to reach his first hardcourt Master Series quarterfinal.
He lost to eventual champion Ivan Ljubičić in a three-set match.
In the 2010 Sony Ericsson Open, he lost in the third round to Fernando González, after defeating Marsel İlhan in the second round.

In the 2010 Monte-Carlo Rolex Masters, he defeated qualifier Jarkko Nieminen for the first time in three meetings and was upset by Michael Berrer in the second round.
His bad run continued as he was upset by Daniel Gimeno-Traver in the first round as the tenth seed of the 2010 Barcelona Open Banco Sabadell.
He defeated Igor Andreev, but lost to Victor Hănescu in the second round of the 2010 Internazionali BNL d'Italia.
In the 2010 Mutua Madrileña Madrid Open, he defeated Simon Greul and Thomaz Bellucci.
He then lost to Nicolás Almagro.
He then led Argentina to their second ARAG World Team Cup.
In the final he defeated American Sam Querrey.
At the 2010 French Open, he was upset by qualifier Grega Žemlja in four sets in the first round.
He then withdrew from the 2010 Wimbledon Championships due to a wrist injury and missed two months of action.
He made his return in the 2010 Western & Southern Financial Group Masters in a losing effort to Thiemo de Bakker.
He then lost in the first round of 2010 Pilot Pen Tennis, the US Open, and the 2010 Rakuten Japan Open Tennis Championships.

In October, he reached an ATP World Tour Masters 1000 semifinal for the first time in the 2010 Shanghai Rolex Masters 1000 by defeating Florent Serra 6–4, 7–6 Thiemo de Bakker 2–6, 6–3, 6–4, Mischa Zverev 6–2, 6–0 and Jürgen Melzer 6–7, 7–5, 6–2, but then lost to World No.
4 Andy Murray 6–4, 6–1.
At the 2010 Valencia Open 500 he upset defending champion Andy Murray 6–2, 3–6, 6–2 in the second round but was then upset by Marcel Granollers 1–6, 6–3, 6–4 in the following round.
Monaco, played his last tournament of the year at the BNP Paribas Masters where he defeated Sam Querrey 6–2, 7–6 but fell to no.
2 seed Novak Djokovic 6–4, 6–3 in the second round after failing to convert 7 of 8 break points.
Monaco started 2010 with the Heineken Open, where he defeated Horacio Zeballos in the first round, but lost to eventual champion John Isner in three sets. He lost to sixth seed Nikolay Davydenko in the third round of the 2010 Australian Open, having defeated Ernests Gulbis and Michaël Llodra in five sets. He lost to Thomaz Bellucci in the final of the 2010 Movistar Open, after defeating Nicolas Massú, Juan Ignacio Chela, Peter Luczak, and João Souza. He lost to Juan Carlos Ferrero in the semifinals of the 2010 Copa Telmex just hours after defeating Horacio Zeballos in the quarterfinals, where he did not face a single break point. He also defeated Juan Ignacio Chela in the second round and Łukasz Kubot. He lost to Juan Carlos Ferrero in the semifinals of the 2010 Abierto Mexicano Telcel, retiring with an abdominal strain. He defeated top seed Fernando Verdasco in the quarterfinals, Juan Ignacio Chela for the second time in as many weeks, and Alberto Martín.
He defeated Fabio Fognini in the second round of the 2010 BNP Paribas Open. He then faced Juan Carlos Ferrero in the third round; this was their third straight meeting, with Ferrero prevailing in the other two. He upset Ferrero for the first time in a match than lasted over 3 hours. He then defeated Guillermo García-López to reach his first hardcourt Master Series quarterfinal. He lost to eventual champion Ivan Ljubičić in a three-set match. In the 2010 Sony Ericsson Open, he lost in the third round to Fernando González, after defeating Marsel İlhan in the second round.
In the 2010 Monte-Carlo Rolex Masters, he defeated qualifier Jarkko Nieminen for the first time in three meetings and was upset by Michael Berrer in the second round. His bad run continued as he was upset by Daniel Gimeno-Traver in the first round as the tenth seed of the 2010 Barcelona Open Banco Sabadell. He defeated Igor Andreev, but lost to Victor Hănescu in the second round of the 2010 Internazionali BNL d'Italia. In the 2010 Mutua Madrileña Madrid Open, he defeated Simon Greul and Thomaz Bellucci. He then lost to Nicolás Almagro. He then led Argentina to their second ARAG World Team Cup. In the final he defeated American Sam Querrey. At the 2010 French Open, he was upset by qualifier Grega Žemlja in four sets in the first round. He then withdrew from the 2010 Wimbledon Championships due to a wrist injury and missed two months of action. He made his return in the 2010 Western & Southern Financial Group Masters in a losing effort to Thiemo de Bakker. He then lost in the first round of 2010 Pilot Pen Tennis, the US Open, and the 2010 Rakuten Japan Open Tennis Championships.
In October, he reached an ATP World Tour Masters 1000 semifinal for the first time in the 2010 Shanghai Rolex Masters 1000 by defeating Florent Serra 6–4, 7–6 Thiemo de Bakker 2–6, 6–3, 6–4, Mischa Zverev 6–2, 6–0 and Jürgen Melzer 6–7, 7–5, 6–2, but then lost to World No. 4 Andy Murray 6–4, 6–1. At the 2010 Valencia Open 500 he upset defending champion Andy Murray 6–2, 3–6, 6–2 in the second round but was then upset by Marcel Granollers 1–6, 6–3, 6–4 in the following round. Monaco, played his last tournament of the year at the BNP Paribas Masters where he defeated Sam Querrey 6–2, 7–6 but fell to no. 2 seed Novak Djokovic 6–4, 6–3 in the second round after failing to convert 7 of 8 break points.
Juan Mónaco