A user with an Exchange mailbox had this question:

In the account properties for my Exchange mailbox, it does not allow me to change the SMTP server, which is automatically configured for the Exchange server. I would like to use a different SMTP server. Is it possible to change?

No, its not possible to change the SMTP when the account is configured in Outlook as an Exchange account. If your server supports IMAP or POP3, you could create the account in Outlook as POP3 or IMAP and use an alternate SMTP server.

Using a SmartHost

On the Administrator side, it is possible to configure the Exchange Server to use another SMTP server, instead of sending the email to the Internet itself. This is called a SmartHost and is commonly used when an on-premises server is used at a small business site and the Internet connection cannot be used directly for outgoing mail for one reason or another.

In this situation, the administrator can set up the Exchange server to use a smart host and set the ISP or email host's SMTP server as the smart host. When you do this, all mailboxes on the server will send their mail through the SMTP set as the smart host. The users Internet addresses are added to their accounts and set as the default SMTP address. When they send mail and it goes out through Exchange, the reply address is their Internet address and replies are route-able.

To set up a smart host, open Exchange Management Console and browse to Organization Configuration, Hub Transport, Send Connectors. Set up the smart host on the Network tab of the Send Connector to send mail to your ISP or mail provider;'s SMTP server.

If the Internet addresses all use the same format for the alias (first.last, last.first, flast, firstl etc) you can configure the addresses to be automatically applied to the user accounts. Otherwise, you'll need to edit each Exchange account or Active Directory account individually.