Chavez Jr. on September 17, announced that he would fight at the full super middleweight limit of 168 pounds against former WBC champion Anthony Dirrell (30-1-1, 24 KOs) at The Forum in Los Angeles, California on November 11, 2017. Three days later, Dirrell spoke out on his local Michigan paper, Mlive, saying "Don't believe that," immediately denying that he had agreed to fight Chavez Jr. On October 10, trainer Nacho Beristain stated that Chavez would return in December 2017. On October 24, Beristain revealed that he could not get in touch with Chavez Jr. regarding their training camp. A new date of December 16 was considered for his new return date to the ring. Beristain stated that Chavez was returning to his hold training habits. He told ESPN Deportes that if he did not hear from Chavez in the next 10 days, he would not be working his corner. On November 14, fellow Mexican Alfredo Angulo (24-6, 20 KOs) was named as a possible opponent as both boxers being advised by Al Haymon. Chavez told ESPN Deportes that he had hoped to reach an agreement with Beristain to work his corner.

In October 2016, it was announced that Chávez Jr. would be making a return on December 10, 2016 at the Monterrey Arena in Mexico against German boxer Dominik Britsch (32-2-1, 11 KOs). A catchweight of 169 pounds was agreed by both fighters. Chávez confirmed he would be trained by his uncle, Rodolfo Chávez. With a win here, Chávez Jr. would look to fight Canelo Álvarez next. Chávez Jr. officially weighed in at 168 pounds, the limit for super middleweight.

Following the loss to Alvarez, Chavez Jr. said he would be making a full comeback at 168 pounds in the super middleweight division. He said he would fight again towards the end of 2017, most likely December. A potential name he had mentioned was former WBA 'regular' middleweight champion Daniel Jacobs. On July 23, Chavez Jr. tweeted that he could return as soon as October 2017 and named Martin Murray (35-4-1,16 KOs) as a potential opponent.

A deal was reached for Chávez and Sergio Martínez (49-2-2, 28 KO) to fight on September 15, 2012, at the Thomas & Mack Center in Las Vegas for the Unified WBC and The Ring Middleweight Championship.

Chávez Jr. picked up his 50th win of his career after defeating Britsch in a one-sided 10 round unanimous decision in front of a very small crowd in Mexico. All three judges scored it 99-91 in favor of Chávez. In the post fight interview, Chávez called out Canelo and Gennady Golovkin, "I am happy with the win and my performance. I am ready to come back in two or three months. I don't need another fight. I am ready for a world title fight with anybody or any other big fight."

This was the first boxing match to generate over 1 million PPV buys that didn't include Mayweather, Pacquiao or De La Hoya since 2002, which saw Lennox Lewis retain his heavyweight world titles against Mike Tyson. Later sources confirmed the fight did close to 1.2 million buys, which means it would have generated around $80 million.

After those amateur fights, Chávez Jr. started his professional boxing career at 17 years old. On September 26, 2003, at Super Featherweight (130 lbs), he won his professional debut by outpointing Jonathan Hernandez over six rounds in Chávez Jr.'s native Culiacán, Sinaloa. Chávez Jr. was signed with Bob Arum's Top Rank. Many of his fights have been held during boxing programs that have been headed by his father; he has also been featured on the undercards of many major pay-per-view fights (rare for an up-and-coming fighter, but not unexpected in his case given his father's fame). He is considerably taller than his father. Chávez Jr. set a fighting pace that was reminiscent of Chávez Sr.'s own pace when the latter was a younger man: in 2004, he fought eleven times, not having a fight only in August during that year.

Chávez won by a split decision over Matt Vanda July 12, 2008. Scores for the fight were 97–93 and 100–90, while losing 96–95 on another card. Chávez struggled with making weight for several bouts and was suspended following his win over Troy Rowland for using a banned diuretic, furosemide, to make the 160-pound weight limit. As a result, the fight was changed to a no contest.

In December 2010, Alfonso Gomez was signed to match up against the undefeated Chávez Jr. at middleweight (the contracted weight was 157) for Chávez Jr's WBC Silver Middleweight belt on the In Harm's Way card as the main event. However, during training for the bout, Alfonso tore some ligaments in his left elbow and had to withdraw from the card and undergo a few months of rehab. For his part, Chávez Jr was set to fight Paweł Wolak as a replacement bout, but after adjusting the weight limit for said match to 165 lbs, Chávez Jr had to pull out due to the flu messing up his training and weight loss and then in January he went on to beat title contender Billy Lyell.

Chávez Jr. successfully defended his Middleweight title with a fifth-round knockout of Peter Manfredo Jr. in Houston on November 19, 2011.

On June 16, 2012, at the University of Texas at El Paso, Sunbowl in El Paso, Texas. Chávez Jr. recovered from a slow start he blamed on leg cramps and stopped Andy Lee at 2:21 of the seventh round to retain the WBC Middleweight title. A right uppercut by Chávez snapped Lee's head upwards and sideways and Chávez connected on a barrage of punches before Referee Laurence Cole intervened and waved an end to the fight. The fight averaged 1.6 million viewers on HBO.

After a year of suspension, Chávez faced Brian Vera on September 28, 2013 at the StubHub Center in Carson, California. Chávez struggled with the weight before the fight and he hardly reached the 172 pounds for a fight pacted in 168 pounds. The night of the fight he weighed 186 pounds. Like the fight against Martínez, Chávez threw very few power punches while Vera dominated the fight. In the late rounds, although Chávez landed the more harder punches throughout the fight. Chávez won a controversial unanimous decision. He threw 320 punches, while Vera threw 734. The decision was heavily criticized by the audience. After the fight, Chávez stated that he fought with an injured hand.

A rematch was held on March the 1st, 2014, at the Alamodome of San Antonio, Texas. Contrary to what happened in the first fight, Chávez came out more aggressive and proposed the fight. He kept the distance with the jab and landed power punches. In the eleventh round he landed a powerful right hand that nearly knocked Vera out. Chávez won via unanimous decision claiming the vacant WBC Continental Americas super middleweight title.

Chávez announced that he would be returning on July 18, 2015 against fellow Mexican Marcos Reyes (33-2, 24 KOs) at the Don Haskins Convention Center in El Paso, Texas in a 10-round super-middleweight bout. Due to Chávez not making weight the fight time, a catchweight of 170 pounds was established. Chávez was fighting for the first time with renowned trainer Robert Garcia. Chávez won a unanimous decision over Reyes with scores off 97-92, 98-91, 96-93. Reyes started each round with more activity and by landing shots. However, Chávez landed three or four heavy shots that moved his Reyes' entire body. The punches seemed to stun Reyes and gave Chávez control of the rounds. The pro Chávez crowd began to jeer his performance during and after the fight.

On January 13, Álvarez officially confirmed the fight to take place on May 6, 2017. A rematch clause was also put in place if Chávez Jr. wins the fight and another clause for every pound Chávez Jr. weighs over the limit, he would be fined $1 million. On February 4, Golden Boy Promotions announced that the fight would take place at the T-Mobile Arena in Paradise, Nevada. The fight was announced a sell out on March 3 with 20,000 tickets being sold after they initially went on sale to the public on February 20.