Data from the Department for Education showed "wilful and repeated transgression of protective measures" was the reason behind the exclusions in 2020-2021.
Overall, 482 students – the majority from secondary schools – were excluded for this in the region, with 478 being temporary and four being permanent.
It has led to the Labour Party criticising the Government's lack of "clear guidance" over pandemic measures which have impacted on children's futures.
Stephen Morgan MP, the shadow schools minister, said: “The Conservatives have created deep divides in school exclusions, with the lack of clear guidance, especially during the pandemic, threatening children’s futures and failing communities.
“The Government’s own independent review highlights the need to tackle exclusions and ensure children are supported in order to improve life chances.
“No parent wants to see their child excluded from school but once again the Conservatives have treated our children and their future opportunities as an afterthought.”
In Wolverhampton, a total of 83 exclusions were made overall, with all of them being temporary. In Dudley, the figure was 111 overall with 110 temporary and one permanent.
Meanwhile in Walsall, 79 exclusions were made, with 77 temporary and two permanent. And in Staffordshire, 145 exclusions were made which were all temporary.
Children across England were excluded 12,965 times for reasons including non-compliance with social distancing, causing distress such as by purposefully coughing near to others, or any other deliberate breach of a school's public health measures.
Julie McCulloch, director of policy at the Association of School and College Leaders, said schools worked very hard to keep pupils and staff safe during the pandemic, and it was not unreasonable that young people should be expected to comply with these measures.
The National Association of Head Teachers said schools following guidance were sometimes forced to suspend students in cases of persistent rule breaking and unsafe behaviour, with school leaders making tough decisions to keep everyone safe.
Paul Whiteman, general secretary of the union, said exclusions are always a last resort – and have fallen to an all-time low across England – but should not mean the end of the road for pupils affected.
He added: "Unfortunately cuts to health and social care services mean that the safety net for excluded young people has too many holes in it.
"This is something that the Government should address urgently.”
A Department for Education spokeswoman said permanent exclusions are a rare but necessary way of managing behaviour – but should not mean exclusion from education.