Geoffrey Bouchard of AG2R Citroën Team took the mountains classification title after consistently taking maximum points on the stages' early climbs.

Other top contenders were Hugh Carthy (EF Education–Nippo), after his third place in the 2020 Vuelta a España, former podium finisher Mikel Landa (Team Bahrain Victorious), Emanuel Buchmann (Bora–Hansgrohe), Aleksandr Vlasov (Astana–Premier Tech), Pavel Sivakov (Ineos Grenadiers), and two Maglia Rosa wearers from the 2020 edition – João Almeida (Deceuninck–Quick-Step) and Jai Hindley (Team DSM), the eventual 2020 runner-up.

[12] The full route, consisting of 21 stages covering a distance of 3,479.9 kilometres (2,162.3 mi) and an elevation gain of over 47,000 metres (154,000 ft), was announced by RCS Sport on 24 February 2021.

[13] However, due to poor weather, the stage was rerouted to remove the Pordoi and Fedaia, significantly shortening it and leaving the Passo Giau as the only climb in the Dolomites.

The sprinter's teams did their work neutralizing and exterminating the breakaway threat, setting up a final sprint where Tim Merlier won the day ahead of Giacomo Nizzolo and Elia Viviani.

Stage 3 began with heavy rain, but despite the conditions an escape bunch of seven riders eventually formed with Albanese among them as he was seeking to defend his mountains jersey, which he was able to do.

With the peloton continuously closing the gap late in the stage Simon Pellaud made an attack and Taco van der Hoorn was the only other rider able to stay with him.

As a result, he was the last man up the road during the final few kilometres and he managed to beat the hard charging peloton to the finish line by just four seconds as Davide Cimolai took 2nd and Sagan settled for 3rd.

Hermans was dropped before long and for much of the day Juul-Jensen and Taramae led the race with Taaramäe being in a position to take the pink jersey if the attack was successful.

Eventually, six riders went clear about 30 kilometres (19 mi) into the stage, while the duo of Geoffrey Bouchard (AG2R Citroën Team) and Bauke Mollema (Trek–Segafredo) soon gave chase and after a considerable pursuit managed to bridge the gap to the break.

It started raining again and more escape attempts came, including a final group of 17 riders, which teams FDJ and Ineos rode to control at the front of the main field.

As the end of the stage approached, the gravel section, the final escapees included Mollema of Trek and Michael Storer of DSM chasing the duo of Koen Bouwman riding for Jumbo-Visma and Bouchard of AG2R.

Bernal then put his stamp of authority on the race[25] by attacking again which Ciccone answered briefly and with 400 metres to go they passed the final breakaway riders like they were standing still.

During the stage Matej Mohorič was involved in a serious crash when he hit a crack in the road and was violently thrown over his handlebars as the front wheel completely broke off his bike.

Cesare Benedetti, Felix Grosschartner and Matteo Fabbro forced the pace through the foothills and Emanuel Buchmann, Giovanni Aleotti and Daniel Oss kept the pressure on throughout the day and several elite sprinters were dropped including Nizzolo, Merlier and Dylan Groenewegen.

With 43 kilometres to go the breakaway was absorbed back into the bunch and while they had run into a spot of bad luck being forced to stop and wait at a train crossing, the race jury determined this wouldn't have changed the inevitability of the peloton eventually catching them.

[27] In the GC situation Aleksandr Vlasov was now the only rider within a minute of Bernal as Damiano Caruso rode strongly and rose in the standings to occupy the final podium position.

There were multiple crashes in the stage which would cause the eventual abandons of Alessandro De Marchi and Marc Soler, who was in 11th place overall when he left the race.

[28] Stage 13 was a return to the flats where the breakaway was limited in number due to the reality of the sprinters' teams being unlikely to give any would-be escapees much chance of success.

Three riders eventually formed an escape group, all of whom were familiar faces in the breakaways thus far in the Giro – Samuele Rivi, Umberto Marengo and Simon Pellaud.

Astana–Premier Tech put in a lot of the work at the front of the main field and was attempting to get Aleksandr Vlasov in a good position for the upcoming climb on Monte Zoncolan.

Edoardo Affini and Jacopo Mosca put in a great deal of work at the front of the breakaway group in an attempt to get their teammates George Bennett and Bauke Mollema the opportunity to go for the stage win.

Jan Tratnik attacked the breakaway group and only Lorenzo Fortunato eventually made the move to go with him although Alessandro Covi, Bennett and Mollema were not far behind initially.

In the end seven riders were within ten seconds at the finish line where Victor Campenaerts of Team Qhubeka Assos narrowly defeated Oscar Riesebeek of Alpecin–Fenix for the stage win.

The GC situation remained the same, but due to the withdrawal of Buchmann Tobias Foss, who had fallen as low as 31st place earlier in the race, entered the top 10.

Vlasov suffered a mechanical at an inopportune time and was dropped from the GC group, Yates was not able to match Bernal's pace, neither was Carthy and Evenepoel came unhinged and lost over twenty minutes by the end of the day.

In the GC situation Almeida crossed the line 2nd, and jumped up to 8th place overall, in the process he became the team leader of Deceuninck–Quick-Step being as Evenepoel had a tough day and would not start stage 18.

With 6.3 kilometres to go Yates also attacked and he was joined by Bennett, Vlasov and Caruso as Jonathan Castroviejo and Martínez made sure Bernal would not fall into danger of losing serious time.

For the next three kilometres Carthy, Vlasov, Bennett and Almeida had fallen back to the Bernal group as Yates struggled to force a gap, but eventually managed to get away.

Caruso had teammate Pello Bilbao to assist him much of the stage as Michael Storer and Romain Bardet of Team DSM were at or near the front of the race for most of the day.