A 30 year old Ortiz made his debut on 16 February 2010, against American boxer Lamar Davis (4–1, 1 KO) in a scheduled 4 round bout at the Seminole Hard Rock Hotel and Casino in Hollywood, Florida.

Ortiz fought again at the Seminole Hard Rock Hotel and Casino for his second professional fight on 15 June against 39 year old Charles Davis.

In his third pro fight, Ortiz claimed the vacant WBC FECARBOX heavyweight title against 28 year old Kendrick Releford (22–13–2, (10 KOs) on 24 August 2010.

Ortiz won his next 2 bouts via eighth-round stoppage against Zack Page and Francisco Álvarez (12–1, 10 KO), improving his record to 5 wins in as many fights, with 4 coming within the distance.

Ortiz fought twice in April, first defeating Jerry Butler via third-round TKO and then knocking out former world title challenger Bert Cooper (38–22, 31 KOs) within 2 rounds.

[6] A month later, Ortiz defended the WBA Fedelatin heavyweight title against Henry Saenz (22–8–1, 18 KOs) at the Gimnasio Nacional in San José, Costa Rica.

[7] In February 2012, Ortiz fought 36 year old Epifanio Mendoza (32–13–1, 28 KOs) at the Community Center in Florida for the vacant WBO and WBC Latino heavyweight titles in a scheduled 10 round fight.

[8] On 3 April 2014, in what was considered as his best and most known opponent in his career to date, Ortiz fought 42 year old former world title challenger Monte Barrett (35–10–2, 20 KOs) at the Fantasy Springs Casino in Indio, California.

Barrett, who was taking this fight on short notice, was hit with a left hand on the nose and went down on his right knee after which referee Caiz stopped the bout without a count.

[12][13][14] On 27 October 2014, the Nevada State Athletic Commission postponed the taking of a decision to potentially change the result to a no-contest until a full hearing was held, as Ortiz was not yet ready to testify on that date.

[15][16] After a 9-month suspension, Ortiz fought on the undercard of world middleweight title fight Lemieux–N'Dam N'Jikam on 20 June 2015, at the Bell Centre in Montreal, Canada, against 35 year old American Byron Polley (27–18–1, 12 KOs).

[18] A year after being stripped, Ortiz had a second chance of becoming Interim world champion, this time against Argentine Matias Ariel Vidondo on the undercard of Golovkin vs. Lemieux on 17 October at Madison Square Garden, New York City.

[20][21] On 21 October 2015, HBO announced that Ortiz would have his first real test against former world title challenger Bryant Jennings (19–1, 10 KOs) on 19 December at the Turning Stone Casino, Verona, New York.

[24][25] After the fight, Ortiz called out fellow heavyweights Deontay Wilder, Tyson Fury and Wladimir Klitschko, stating he was ready to prove himself as the best in the division.

[28] On 9 February 2016, it was announced that Ortiz would defend his WBA Interim title against veteran heavyweight Tony Thompson (40–6, 27 KOs) at the DC Armory, in Washington on 5 March.

[39] The following day it was confirmed that Ortiz would be fighting for the vacant WBA Inter-continental heavyweight title in the ‘Monte-Carlo Boxing Bonanza’ main event against American Malik Scott (38–2–1, 13 KOs) on 12 November.

Allen commented on the match-up, "I don’t think he's what he's hyped up to be, but I will give him more opportunity than Malik Scott to show he is the real deal, I’ll stand in front of him and see what he's about.

[45] Following the win against Allen, Ortiz was named mandatory challenger for the winner of the WBA (Super), IBF and IBO unification bout between Anthony Joshua and Wladimir Klitschko.

[48][49] A day later it was revealed that he would be part of the 22 April undercard of the Shawn Porter vs Andre Berto world title eliminator at the Barclays Center, New York, against 36 year old journeyman Derric Rossy (31–12, 15 KOs) in a scheduled 10 round bout.

[52][53] Stiverne announced he had hired James Prince and attorney Josh Dubin as his managers, who were best known to have worked for Andre Ward, Shakur Stevenson and Bryant Jennings.

Stiverne told Boxing Scene that Don King had not been given any permission to negotiate a step aside fee and he would work with his management team to ensure he challenges for the WBC title in his next fight.

[59] It was reported on 29 September 2017, Ortiz had failed a drug test carried out by VADA, part of the WBC clean fighters programme.

He said, "The WBC will schedule a visit with one of their approved physicians to check Luis' health, and make sure he is 100% healthy and fit to fight, and that the blood pressure pills will not affect him physically.

[66] WBA president Gilberto Mendoza later stated that the longevity of the ban was also due to Ortiz being a repeat offender, having previously failed a test in 2014 for anabolic steroids.

Referee David Fields kept a close eye on Wilder, who at one point, looked to be almost out on his feet, but managed to make it to the end of the round.

Ortiz dominated every round leading to the stoppage, however Kauffman was always standing in front of him and showed a good chin and heart, even switching to the southpaw stance, where he had some success.

After Kauffman beat the count, Ortiz piled on the pressure with numerous power shots, mostly unanswered, forcing referee Thomas Taylor to step in and stop the fight.

[101] On 16 January 2019, it was announced that Ortiz would next fight German heavyweight contender Christian Hammer (24–5, 14 KOs) 2 March at Barclays Center in Brooklyn, New York.

[108] On November 15, 2021, it was revealed by ESPN that Ortiz and one-time IBF heavyweight titleholder Charles Martin had come to an agreement to face each other on January 1, 2022, after both fighters had spent the entire 2021 without a single fight.

Although Martin was able to beat the ten count, he was quickly knocked down for the second time after the action resumed, which prompted the referee to wave the fight off.