His victories in 2009 in Soruluze, Gorla or Murguía made him sign as a professional with the Orbea team, the then subsidiary of Euskaltel Euskadi. In 2010 he demonstrated his quality finishing fifth in the Tour del Porvenir. His good work made him be promoted to Euskaltel Euskadi in 2011.
In the season of his debut in the elite, he won his first victory as a professional in the Lagunas de Neila, in the Queen stage of the Vuelta a Burgos, demonstrating his potential. He raced his first monument, although he did not manage to finish Il Lombardia.
In 2012 he did not draw too much attention, finishing second in the Gran Premio Miguel Induráin and finishing fourth in the Vuelta a Madrid. He raced his first major, the Vuelta a España, finishing 69th. In 2013, his last season with Euskaltel Euskadi, in the team he claims he is going to retire, he was sixth in the Vuelta a Burgos, second in the Vuelta a Madrid, second in the Vuelta a Asturias and finished 39th in the Vuelta a España. He raced Il Lombardia again and this time finished 21st. He committed to the Astana team.
In 2014 he made his debut at the Tour de San Luis in his new Astana colors. He got his first win with the Kazakh team at the Giro del Trentino, a race he finished tenth in before racing his first Giro d'Italia, in which he did not stand out. He was third in Lagunas de Neila in the Vuelta a Burgos before finishing 28th in the Vuelta a España.
2015 was the year of his consolidation in the elite of world cycling. He won a stage in the Itzulia, finished second in the Giro del Trentino and won 2 stages and finished third in the Giro d'Italia, where he helped Fabio Aru in the battle against Alberto Contador, but proved himself as a top world climber as well. To top off his season he won a mountain stage in the Vuelta a España.
In 2016 he signed for Team Sky again won a stage at the Tour of the Basque Country and took another stage and the overall at the Giro del Trentino. However, he had to abandon the Giro d'Italia due to a crash. He returned in Dauphiné, where he finished tenth and rode the Vuelta a España at the end of the season, but did not perform at a good level (he finished 35th).
In 2017 Mikel started off finishing sixth in the Vuelta a Andalucía and then was not too fortunate neither in Tirreno Adriatico nor in the Volta a Catalunya. In an irregular Giro d'Italia he ended up winning the last stage with a summit finish and taking the mountains jersey. He then rode his first Tour de France, where he performed at a very high level and finished fourth, just one second behind Romain Bardet in third place.
In 2018, at Movistar Team after 2 years at Sky, Mikel was sixth in Andalusia, sixth in Tirreno, second in the Itzulia, 16th in Switzerland and returned to race the Tour de France, finishing seventh. He started 2019 with a stage win in Settimana Coppi e Bartali before finishing seventh in the Itzulia and Liège-Bastogne-Liège. He raced the Giro d'Italia again, finishing fourth, and the Tour de France, finishing sixth. He left Movistar and signed for Bahrain Victorious at the end of 2019.
He started 2020 with a third place in Andalusia and a second in Burgos. He passed without glory in Dauphiné before coming close to the podium again in the Tour de France. He was again fourth, though this time more than two minutes behind Richie Porte.
In 2021 he dropped out of both the Giro d'Italia and the Vuelta a España. A podium in Tirreno Adriatico was the highlight for him. In 2022 he was third again in Tirreno and got another podium in the Giro d'Italia, finishing third behind Jai Hindley and Richard Carapaz. In the Vuelta a España he couldn't shine and finished 15th. However, he finished the season well with a third place in Il Lombardia.