A 350-tonne crane will lift sections of the new Deansgate-Castlefield Metrolink stop track into place this weekend.
Transport for Greater Manchester said the major transformation works at the stop started earlier this year and will allow more flexible and frequent services to run through the city centre.
The Deansgate-Castlefield stop will be closed on Saturday and Sunday and – to make way for the crane – Whitworth Street West will be closed from Deansgate to Albion Street from 8pm Friday 25 July to 4am Monday 28 July.
Bus services 84, 255, X50 and Metroshuttle 2 will follow the diversion route.
Access to local car parks and businesses will be maintained at all times and the taxi rank will be temporarily located between Deansgate and Bugle Street.