TeX Live 2014 on Xubuntu 14.04 LTS, compiling with xelatex.
Minimal working example:
\documentclass[11pt, twoside]{book}
\usepackage{geometry}
\geometry{a4paper, left=3.5cm, right=2.5cm, top=3.5cm, bottom=3.5cm}
\usepackage{fontspec}
\setmainfont[Mapping=tex-text]{Linux Libertine O}
\setmonofont{Linux Libertine Mono O}
\usepackage{lipsum}
\usepackage{afterpage}
\begin{document}
\mainmatter
\lipsum[1-3]
\afterpage{
\clearpage
Here be landscape content.
\clearpage
}
\lipsum[4-5]
\paragraph{Paragraph Title}
Text spanning this and the two next lines. Text spanning this and the two next
lines. Text spanning this and the two next lines. Text spanning this and the
two next lines. Text spanning this and the two next lines. Text spanning this
and the two next lines.
\paragraph{Paragraph Title}
Text spanning this and the three next lines. Text spanning this and the three
next lines. Text spanning this and the three next lines. Text spanning this
and the three next lines. Text spanning this and the three next lines. Text
spanning this and the three next lines. Text spanning this and the three next
lines.
\paragraph{This paragraph breaks uglily}\label{mrkr}
\lipsum[2]
\end{document}
The document looks like this, mind the manually added labels for some explanation:

The first \paragraph to appear after \afterpage is cut into its run-in heading residing on its own page and the remainder after the \afterpage. What am I doing wrong?
PS: I had to add my own dummy paragraphs, because it was too cumbersome trying to get the right height with the \lipsum paragraphs.

\paragraphand the text after it; the\paragraphmust be at the end of a page, the text after it should break; the\paragraphmust be preceded by at least one other\paragraphwith some text. That would also explain why you are not seeing the problem with a\ruleand without the font. – Kreuvf Dec 10 '15 at 13:27