The regional airline said the staff shortage plus a “combination of factors” caused the disruption.
The 7.20am departure to Southampton was cancelled along with 1.20pm from Manchester, while a 7am flight to Birmingham was delayed until 8.35am.
Of the Flybe arrivals at Edinburgh Airport, the 8.10am from Cardiff touched down at 9.15am, while the 9.55am from Birmingham now expects to arrive at 11.30am.
One disgruntled passenger took to Twitter to vent his frustration. @lamchops1987 wrote: "Very much doubt I will be using Flybe again. Flying from Edinburgh this morning: Birmingham 0700 delayed. Southampton 0729 cancelled Cardiff 0840 delayed Heathrow 0850 delayed Manchester 1020 cancelled. I’ll be late for my meeting today! Cancellations on way back too!"
Aberdeen International Airport has also been affected, with the 10.40am arrival from Birmingham cancelled, along with the 11.55am from Humberside and the 1.50pm from Belfast.
Elsewhere, a number of flights from Belfast Airport have been affected and most of the routes are thought to be flights within the UK.
A spokesperson for Flybe said in a statement: "Flybe sincerely apologises to all our customers and partners affected by the current flight cancellations. Whilst 95% of Flybe flights are operating as per normal, we do recognize the impact of today’s cancellations.
"We are doing our best to mitigate the impact of the current situation that has arisen due to a combination of factors including seasonality, pilots’ end of leave year, Easter holidays, base restructuring and the shortage of pilots across the industry that Flybe has highlighted over recent months.
"We have already identified several mitigation actions and will be issuing further updates throughout the day.
"All those affected have been emailed and advised they can re-book for travel on an alternative flight or apply for a full refund.
"Customers are advised to regularly check our website for more details."