Help with my itinerary.

It is a good plan!
What you could do, perhaps, is head straight to Toledo upon arrival and spend 2 nights there, then head to Barcelona the following morning. That way, you'd have all your Madrid days at the end. And Toledo is nice in the evening, it deserves more than a day trip.

I suspect when you say "2-3 days" in Seville you mean 2-3 nights--right? That's only 1-2 full days, which isn't enough for Seville. I think 4 nights is about the minimum for Seville, and that's with no day trips.

You didn't mention Cordoba, which is a lovely destination.

Toledo and Segovia are both highly recommended.

Personally, I don't believe you're likely to need 7 ( or even 6) nights in Madrd, despite planning 2 day trips, unless you want to spend a great deal of time in its art museums. I'd move some of that time to Cordoba and Seville.

I a gree that it would be far better to consolidate all your Madrid nights at the end of the trip. Traveling on to Toledo on your arrival day would be easy.

Love all the suggestions. So on reflection, there is my plan:
Arrive Madrid, travel on to Toledo (2 nights), train to Barcelona (4 nights) with 1 day trip to Montserrat, fly to Granada (2 nights), train to Seville (4 nights), train to Madrid (4 nights) with 1 day trip to Cordova. Does that sound do-able? Also any thoughts on November travel time? We don't mind if it on the cool-ish side. Will we have any issues getting into top tourist sites during that time?

Many travelers overlook how large that Spain is. We went to inland Spain before the pandemic and my wife liked it so well she and her daughter went back 3 months later. I honestly never realized how inexpensive travel was in Spain, especially when compared with other popular Western European countries.

We have been on a number of trains in Europe, and I'm okay for the first 4 hours. Otherwise, I'm trying to find a budget European airline to travel. They've opened up the continent to cheap travel from city to city.

We flew into Madrid and found it to be a great city worthy of at least 4 days on the ground. We then took a bus just over 3 hours down to Granada and found it to be a 3 day city. Alhambra alone is a full day's travel site and a quite physical one at that to see. From there we flew for less than $100 over to Barcelona and it's a 4-5 day city. Our granddaughter wanted so see Paris so we took the 6.5 hour fast train (185 mph tops) up to Paris for 5 days.

You might be pushing it to see Seville as it's pretty far west. For the longer distances within Spain, check out the budget airlines. Vueling flies from Madrid to Barcelona. Ryanair and Iberia fly throughout the region extensively.

Honestly I'd skip Barcelona and just focus on Madrid and Andalucía. I don't think backtracking all the way north to Barcelona is worth all the effort, especially if it forces to add a domestic flight halfway through your trip. Barcelona can always be easily added to a visit to northern Spain, don't try to see it all this trip, Spain is the second largest country in the EU!

I'd also add a night or two to Córdoba, my favorite city in Andalucía! I also penciled in some of my recommend daytrips.

So to recap I'd make a loop starting and ending in Madrid:
Arrive Madrid
Toledo (2 nights)
Cordoba (3 nights) - day trip to Medina Azahara (Caliph's Palace)
Granada (3 nights) - day trip to Antequera (Megalithic tombs)
Sevilla (4 nights) - day trip to Cadiz
Madrid (4 nights) - day trip to Segovia
Fly out of Madrid

hope this helps :)

If you're going to treat Cordoba as a day trip, that trip should be taken while you're in Seville (as little as 41 min. away by train) rather than from Madrid (at least 1 hr. 42 min. by train).

It is not logical to fly between Marid and Barcelona when the train will get you from city center to city center in as little as 2 hr. 30 min. Flying Granada to Barcelona isn't a bad idea, I guess, if your time is so tight that every hour matters. And there aren't a lot of express-train departures from Granada that connect well with trains to Barcelona. I suspect a flight is more likely to be canceled or significantly rescheduled than a train, though.

That is doing quite a lot on your visit. Definitely don't miss a day trip to Toledo. Segovia is great, but what do you have planned for Madrid. Are you doing the Royal Place or the Prado art museum?

You might trim one day from Barcelona to give you more time.

Our favorite month to visit Spain is October.

Barcelona is short as it is--just 3 full days with a day trip to Montserrat. I certainly wouldn't reduce that by one day. Many of the top sights in Barcelona effectively require pre-purchaes of time-specidic tickets because the ticket-purchase lines are so long and are likely to yield a ticket for hours later. The need to guess at what time you can safely plan to be at your second sight, and how long lunch will take, tends to produce a sightseeing schedule with gaps in it, otherwise known as "dead time" from the perspective of a traceler trying to squeeze in the maximim number of sights.

We didn’t add a visit to Barcelona until our third trip to Spain. Then we spent a full week there.

Carlos has given you great advice. You will use up too much time getting to/from Barcelona for not nearly enough time there, while short-changing every stop in Andalucia.